There are factors related to a person and a clinical interaction that produce biological effects without directly affecting the underlying pathophysiology of a disease. The term placebo effects, although not ideal, is used to describe these non-specific effects. Placebo effects was specifically listed as a potential theme in the RFA to which this proposal is responding. Despite varying opinions about the size of placebo effects because of significant methodologic problems, the biologic basis of placebo effects is starting to be understood. It is very important to continue to define and understand these non-specific effects in order to: develop strategies that maximize these beneficial effects;improve clinical trial design;and gain insight into mechanisms of mind- body medicine. This proposal contains 4 projects that will develop models of placebo effects with objective markers and will explore predictors of placebo resonses. The proposal will take advantage of current knowledge in neuroscience and psychology to explore this area, including markers for hypothalamic-pituitary-adrenal axis activity and genetic polymorphisms affecting neurotransmitter function. These assessments as well as good communication between all coleaders will provide synergy across the projects. The interchange with non-human researchers is important to clinical research and this center proposal includes 1 animal model of placebo effect. This developmental center will lead to future projects that will follow on the planned research potentially using other techniques such as RNA expression, neuroimaging, and further neuropharmacology, but believe that the model development and initial exploration of predictors of placebo responses are the critical pieces that can be reliably achieved over the 3 year developmental funding period. This proposal constitutes a unique collaborative effort by Oregon Health &Science University, the National College of Naturopathic Medicine, the Oregon College of Oriental Medicine and Western States Chiropractic College. These institutions have already had ongoing collaborative arrangements. The Developmental Centers for Research on CAM U19 mechanism will strengthen these collaborations and further establish research infrastructure at the CAM institutions with a very promising exploration intoan area of mind-body medicine that is of critical importance to CAM and all conventional medicine.